Method of using lectins for therapy of diseases transmittable by sexual contact

ABSTRACT

In order to prevent conception and/or the spread of sexually transmitted diseases (STD&#39;s) one or more lectins capable of binding sperm and/or the pathogenic microorganisms responsible for STD&#39;s are administered to the vagina prior to sexual intercourse. The lectins immobilize the sperm to render them incapable of fertilization and also bind to the microorganisms to render them non-pathogenic or to the cells to prevent infection by the microorganisms. Lectins can also be administered to treat sexually transmitted vaginal infections. The invention also encompasses a device for to be placed in the vault of the vagina which comprises a ring which surrounds the cervix and a membrane spanning the central aperture of the ring to prevent the direct contact of ejaculate with the cervical tissues. The device is impregnated or coated with lectins and releases them into the vaginal environment over a period of time.

RELATIONSHIP TO OTHER APPLICATIONS

[0001] This application is a continuation-in-part of copending U.S.application Ser. No. 08/938,831, filed Sep. 26, 1997, which is acontinuation of U.S. application Ser. No. 08/759,517, filed Dec. 4,1996, abandoned, which is a continuation of U.S. application Ser. No.08/609,104, filed Feb. 29, 1996, abandoned, which is a continuation ofU.S. application Ser. No. 08/462,666, filed Jun. 5, 1995, abandoned,which is a divisional of U.S. application Ser. No. 08/317,599, filedOct. 3, 1994, abandoned, which is a continuation-in-part of U.S.application Ser. No. 08/130,190, filed Oct. 1, 1993, abandoned.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] This invention relates generally to methods of contraception andprophylaxis against diseases transmittable by sexual contact and therapyof such diseases, and more particularly to a method using intravaginallyadministered lectins for contraception and to protect against thetransmission of diseases that are transmissible by sexual contact and totreat such diseases. The invention also relates to devices forintravaginal administration of lectins.

[0004] 2. Brief Summary of the Prior Art

[0005] Sexually transmitted diseases (STD's) are epidemic in thiscountry and worldwide. Furthermore, other diseases that have nottraditionally been considered to be STD's have also been found to betransmitted by sexual contact, e.g., hepatitis B. The medical and publichealth problems associated with these epidemics have motivated a searchfor methods of controlling these diseases by limiting their transmissionfrom person to person. Similarly, although many methods of contraceptionhave been employed, no universally satisfactory method has beendeveloped.

[0006] Hitherto it has been generally agreed that barrier methods whichprevent the contact of body fluids between individuals are the mosteffective means of preventing transmission of such diseases. Suchbarrier methods are also effective contraceptive procedures. However,such methods are somewhat inconvenient and require some cooperationbetween individuals.

[0007] An alternative method for preventing the transmission of sexuallytransmitted diseases is to kill the pathogenic microorganisms in semenand vaginal secretions so that they are incapable of invading thetissues and causing the disease. While intravaginally placedspermatocides have been used for contraception, alone or in combinationwith barrier methods, antimicrobial materials have not been so used toprevent STD's, probably because many of such materials are irritating toadjacent tissues.

[0008] Administration of biologically active materials to the vagina forwhatever purpose is usually accomplished by the use of some device thatprovides for convenient application of the medication by the userherself. A variety of devices exist for delivery of bioactive substancessuch as spermatocides and various medications. Each has its place in themedical armamentarium but each has certain deficiencies for applicationof contraceptive or anti-microbial agents in the context of sexualactivity. Conventional vaginal suppositories and ovules may not providemedication to the entire vagina because of their shape and placement bythe user in the vagina. Such suppositories are generally comprised of amaterial that melts at body temperature to allow the medication tospread and contact the tissues. However, when the dosage form melts, themedication may drain out of the vagina rather quickly, thus minimizingits potential effectiveness and significantly reducing the extendedexposure of the tissues and pathogens to the medication which is oftennecessary for effective treatment. Similarly, the effective duration ofcontraceptives applied in this way tends to be relatively brief. Inaddition, such delivery vehicles, even when freshly applied, do notprovide any physical barrier to deposition of male ejaculate on thecervix. Such ready access of sperm to the cervix may allow them toescape the action of spermatocides that are diffused throughout thevagina. Furthermore, because cells at the cervix are uniquely sensitiveto several pathogens such as Chlamydia trachomatis, the absence of abarrier deprives these cells of a significant means of protection.

[0009] In order to provide for a longer retention of medication in thevagina and assure a more continuous delivery of active ingredients tothe tissue, several types of vaginal rings have been proposed. Suchdevices are disclosed, for example, in Duncan, U.S. Pat. No. 3,545,439;Roseman, U.S. Pat. No. 3,920,805; Schopflin, U.S. Pat. Nos. 4,012,496and 4,012,497; Wong et al., U.S. Pat. Nos. 4,237,885 and 4,286,587; andNash et al., U.S. Pat. No. 4,292,965. The vaginal rings are generallyimpregnated with a spermatocide and are designed to be retained in thevaginal vault and to release the spermatocide slowly over a period oftime to maintain an effective contraceptive concentration of the activematerial in the vagina. However, such devices do not prevent the directcontact of ejaculate with the tissues of the cervix, and therefore donot protect those tissues from contact with pathogenic organisms whichmight be contained in the ejaculate. They are also of questionableefficacy in supplying the spermatocide where it is most needed.

[0010] Another approach is to use a cervical cap or a diaphragm to serveas a mechanical barrier to the sperm and to dispense medication. Thesedevices are designed for a relatively tight fit either to the cervix orthe walls of the vagina to serve as a mechanical barrier to the passageof sperm. Such devices can be effective, especially as contraceptivesand when combined with spermatocides. However, because of the need toprovide a sperm-resistant seal they are frequently relatively complexdevices incorporating metallic springs within a rubber or syntheticresin structure to provide the required sealing force.

[0011] Another approach to providing an effective concentration ofspermatocide in the vagina is to provide a sponge impregnated with aspermatocide. Such applicators are not intended to be precisely locatedand may permit the contact of ejaculate with the tissues of the cervix,with the undesirable consequences outlined above.

[0012] Accordingly, a need has continued to exist for a method ofcontraception and prophylaxis against STD's by vaginal administration ofa spermatocide and/or antimicrobial material, and for a simple andeffective device to protect the tissues at risk from contact withmicroorganisms while dispensing a spermatocidal and/or antimicrobialmaterial.

SUMMARY OF THE INVENTION

[0013] This need has now been alleviated by the method and device ofthis invention, according to which one or more lectins capable ofbinding sperm and/or the pathogenic microorganisms responsible for STD'sare administered to the vagina or site of infection prior to sexualintercourse. The lectins immobilize sperm to render them incapable offertilization and also bind to the microorganisms to render themnon-pathogenic or to the cells to prevent infection by themicroorganisms.

[0014] The invention also encompasses a device for to be placed in thevault of the vagina which comprises a ring which surrounds the cervixand a membrane spanning the central aperture of the ring to prevent thedirect contact of ejaculate with the cervical tissues. The device isimpregnated or coated with lectins and releases them into the vaginalenvironment over a period of time.

[0015] Accordingly, it is an object of the invention to provide animproved method for prophylaxis against sexually transmitted diseases.

[0016] A further object is to provide a method of contraception.

[0017] A further object is to provide a method for binding andimmobilizing pathogenic microorganisms in the vagina.

[0018] A further object is to provide a method for treating vaginalinfections.

[0019] A further object is to provide a device for delivering lectins tothe vagina over a period of time.

[0020] A further object is to provide an intravaginal device thatprotects the tissues of the cervix from direct contact with ejaculate.

[0021] Other objects of the invention will become apparent from thefollowing detailed description when considered in conjunction with thedrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0022]FIG. 1 is a top plan view of a lectin-delivery device according tothe invention.

[0023]FIG. 2 is a bottom view of the lectin-delivering device of FIG. 1.

[0024]FIG. 3 is a cross section of the lectin-delivering device of FIGS.1 and 2, taken along the line 3-3.

[0025]FIG. 4 is a top plan view of another embodiment of thelectin-delivering device of this invention.

[0026]FIG. 5 is a bottom view of the lectin-delivering device of FIG. 4.

[0027]FIG. 6 is a cross section of the lectin-delivering device of FIGS.4 and 5, taken along the line 6-6.

DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS

[0028] Lectins are carbohydrate-binding proteins of nonimmune originthat agglutinate cells or precipitate polysaccharides orglycoconjugates, i.e., proteins or lipids conjugated to oligo- orpolysaccharides. They are widely distributed, and have been isolatedfrom both plant and animal sources. Their reactions with living cellsare based on their ability to bind with antibody-like specificity toparticular arrangements of the sugar residues that make up oligo- orpolysaccharides.

[0029] The surfaces of eucaryotic cells contain very numerous moleculesof glycoproteins and glycolipids. Similarly, the cell walls and outermembranes of bacteria and the envelopes of viruses contain structuralpolysaccharides and/or glycoproteins. The carbohydrate moieties of thesemolecules which are displayed on the cell surfaces exhibit great varietyin composition and structure that serves to distinguish the types ofcells and to serve as a signal to other cells or materials which comeinto contact with the cell. For, example, variation in the carbohydratemoieties of glycoproteins and glycolipids in the membrane of red bloodcells serves as the basis for the conventional blood typingclassification. When lectins recognize and bind to certain carbohydratemoieties they may serve to cross-link and agglutinate the cells bearingthe binding groups, a property that earns for them the alternate name ofagglutinins. Furthermore, because the same sort of carbohydrate moietiesoften serve as attachment points for pathogens to bind to target cellsand invade them, lectins may block infection of target cells by blockingthe sites used by pathogens as recognition markers. The same type ofspecific binding occurs between sperm and egg in conception, and can beblocked by lectins. The binding ability of lectins may be very specificfor certain mono- or oligosaccharides, allowing lectins to be used as apowerful tool for investigating the oligosaccharide epitopes on thesurface of organisms or cells. Lectins can distinguish between bloodcells of specific blood type, malignant from normal cells, and amongspecies and genus of organisms. While glycoproteins, glycolipids, andbacterial cell walls are believed to be the main lectin-bindinglocations on the surface of cells, it is not excluded that carbohydratemoieties derived from other molecules or cellular structures may bedisplayed on the cell surface or that other lectin-binding structuresmay be present on cell surfaces. All such lectin-binding structures maybe targets for the lectins used in the method of this invention.

[0030] Current medical uses of lectins include distinguishingerythrocytes of different blood types (blood typing). More recently,lectins have been used ex-vivo in depleting T cells of patientsundergoing bone marrow transplantation.

[0031] In the context of this application the term microorganismincludes any microscopic organism within the categories of algae,bacteria, fungi, parasites (helminths, protozoa), viruses, and subviralagents.

[0032] Among the microorganisms that are bound by certain lectins areinfectious organisms such as bacteria, protozoa, and viruses. Lectinsmay be used to identify such microorganisms in vitro and are alsocapable of binding to them in vivo, thereby preventing them frominfecting living cells. Human disease-causing organisms (and thediseases caused by them) that can be bound by lectins include Neisseriagonorrhoeae (gonorrhea); Chlamydia trachomatis (chlamydia,lymphogranuloma venereum); Treponema pallidum (syphilis); Haemophilusducreyi (chancroid); Calymmatobacterium granulomatis (donovanosis);Mycoplasma pneumoniae, M. hominis, M. genitalium, Ureaplasma urealyticum(mycoplasmas); Shigella flexneri (shigella); Salmonella typhi, S.choleraesuis, S. enteritidis (salmonella); Campylobacter fetus, C.jejuni (campylobacter); human immunodeficiency virus HIV-1 and HIV-2(HIV, AIDs); HTLV-1 (T-lymphotrophic virus type 1); herpes simplex virustype 1 and type 2 (HSV-1 and HSV-2); Epstein-Barr virus;cytomegalovirus; human herpesvirus 6; varicella-zoster virus; humanpapillomaviruses (many types) (genital warts); molluscum contagiosum(MSV); hepatitis A virus, hepatitis B virus (viral hepatitis);Trichomoniasis vaginalis (trichomoniasis); yeasts such as Candidaalbicans (vulvovaginal candidiasis), Phthiris pubis (crab louse), andSarcoptes scabiei (scabies). Other diseases that are transmitted bycontact with bodily fluids may also be transmissible by sexual contactand are capable of being prevented by administration of lectinsaccording to this invention. Accordingly, the term sexually transmitteddiseases (STD's) is to be interpreted in this application as includingany disease that is capable of being transmitted in the course of sexualcontact, whether or not the genital organs are the site of the resultingpathology.

[0033] Inasmuch as lectins are also capable of agglutinating human spermand other components of the male ejaculate, and thereby rendering thesperm immobile, intravaginal administration of lectins can also serve asa method of contraception.

[0034] According to the invention a dose of lectins adapted to bind andagglutinate pathogenic microorganisms and/or block the recognition siteson target cells is administered to the vagina prior to sexualintercourse. For therapy of sexually transmitted diseases, the dose oflectins may also be administered at other times in a regimen oftreatment. The active ingredients may also include lectins capable ofbinding and/or inactivating sperm or the male ejaculate to serve as acontraceptive.

[0035] Because of the specificity of lectins for certain microorganisms,it is preferred to administer a mixture of lectins chosen for theirproperties of agglutinating specific pathogens. It is also according tothe invention to administer a mixture of sperm-agglutinating lectins andlectins capable of binding to pathogenic organisms to providesimultaneous contraception and protection against infection.

[0036] A representative listing of lectins, the abbreviations by whichthey are referred to, and their sources is given in Table 1. TABLE 1Lectins and Abbreviations Lectin Source AAnA Anguilla anguilla (eelserum) AAurA Aleuria aurantia (orange peel fungus) ABA Agaricus bisporus(mushroom) ABrA Amphicarpanea bracteata (hog-peanut) AEP Aedopodiumpodagraria (ground elder) AL Hippaestrum hybrid (amaryllis bulbs) APAAbrus precatorius (jequirity bean) AS Avena sativa (oat) BDA Bryoniadioica (white bryony) BPA Bauhinia purpurea alba (camel's foot tree) CACymbidium species CA Colchicum autumnale (meadow saffron) CAA Caraganaarborescens (Siberian pea tree) CCA Cancer antennarius (California crab)ConA Concanavalia ensiformis (jack bean) CPA Cicer arietinum (chick pea)CSA Cytisus scoparius (Scotch broom) DBA Dolichos biflorus (horse gram)DSA Datura stramonium (jimson weed, thorn apple) ECA Erythrinacrystagalli (coral tree) ECorA Erythrina coralldendron (coral tree) EEAEuonymus europaeus (spindle tree) EHA Eppactus hellebrine EHA Eranthishyamalis GNA Galanthus nivalis (snowdrop bulb) GSA-I/GSA-II Griffoniasimplicifolia HAA Helix aspersa (garden snail) HHA Hippeastrum hybridHPA Helix pomatia (Roman or edible snail) JAC (Jacalin) Artocarpusintegrifolia (jackfruit) LAA Laburnum alpinum LBA Phaseolus lunatis(also limensis) (lima bean) LCA (LcH) Lens culinaris (lentil) LEALycopersicon esculentum (tomato) LFA Limax flavus (garden slug) LOALathyrus oderatus (sweet pea) LDA Listeria ovata LTA (LOTUS) Lotustetragonolobus (asparagus pea) MAA Maackla amurensis (maackla) MIHMangifera indica (mango) MPA Maclura pomifera (osage orange) NPL (NPA)Narcissus pseudonarcissus (daffodil) ORS Oryza sativa (rice) PAA Perseaamericana (avocado) PHA (PHA-L) Phaseolis vulgaris (red kidney bean) PNAArachis hypogaea (peanut) PSA Pisum sativum (pea) PWA Phytolaccaamericana (pokeweed) PTAgalactose Psophocarpus tetagonolobus (wingedbean) PTAgalNac Psophocarpus tetagonolobus (winged bean) RCA-I/RCA-IIRicinus communis (castor bean) RPA Robinia pseudoaccacia (black locust)SBA Glycine max (soybean) SJA Sophora japonica (Japanese pagoda tree)SNA Sambuccus nigra (elderberry) STA Solanium tuberosum (potato) TKATrichosanthes kinlowii (China gourd) TL Tulipa sp. (tulip) TMT Tomentine(seaweed Codium tomentosum) UDA Urtica dioica UEA-I/UEA-II Ulexeuropaeus (gorse or furz seeds) URD Urtica dioica (stinging nettle) VAAViscum album (European mistletoe) VFA Vicia faba (fava bean) VGA Viciagraminea VRA Vigna radiata (mung bean) VSA Vicia sativa VVA Viciavillosa (hairy vetch) WFA Wisteria floribunda (Japanese wisteria) WGATriticum vulgaris (wheat germ) suc-WGA (sWGA) Succinyl WGA

[0037] For example, N. gonorrhoeae is agglutinated by lectins that bindto N-acetyl-D-glucosamine residues on their surfaces. Such lectinsinclude WGA and STA, which are known to agglutinate all 193 clinicalisolates of N. gonorrhoeae. WGA is effective for such agglutination at aconcentration of 3.1 micrograms per milliliter. Other lectins showingsome agglutination activity with respect to N. gonorrhoeae includeRCA-I, RCA-II, GSA-I, and SBA.

[0038] Certain species of Chlamydia (trachomatis, psittaci, andpneumoniae) are known to be bound by the lectins ConA, DBA, UEA-1, SBA,and PNA. WGA also binds to the receptors on certain cells, therebyblocking infection by C. trachomatis and C. psittaci.

[0039] PHA binds to several isolates of H. ducreyi, suggesting thatN-acetyl-D-glucosamine is present in the cell envelope polysaccharide.WGA has been found to agglutinate a variety of bacterial cells,including Escherichia coli, Micrococcus luteus, and some types ofStaphylococcus aureus. WGA, specific for N-acetyl-D-glucosamine and SBA,specific for N-acetyl-D-galactosamine, are capable of agglutinating themany bacterial species which contain these sugar residues in their cellwall polysaccharides.

[0040] Various lectins are capable of binding to certain glycoproteinspresent in the envelope of HIV virus. For example, ConA has been foundto block infection of certain cell lines against infection by HIV invitro, and conglutinin, a lectin derived from bovine serum, has beenfound to bind to the HIV envelope precursor protein gp 160, therebypreventing attachment to CD-4 receptors of target cells in vitro. GNAhas been found to prevent infection of T-cells by HIV in vitro.Consequently, ConA, GNA and WGA have been found to be effective atpreventing infection of target cells by HIV-1 and HIV-2 in vitro. NPLand conglutinin have shown some activity as well.

[0041] HPA, ConA, BPA, and EHL have demonstrated efficacy in theprevention of infection of target cells by HSV-1 and HSV-2.

[0042] Lectins are also useful in aggregation of sperm. PHA, WGA, sWGASTA, ConA, PSA, APA, ECA, ECorA have demonstrated varying degrees ofefficacy in agglutination of sperm. While the lectins discussed aboveand the microorganisms and/or sperm against which they are effective arerepresentative of useful lectins according to the invention, it is to beunderstood that other lectins may be discovered which are active in thebinding and agglutination of sperm and of the pathogens of sexuallytransmitted diseases, and that the use of such lectins is intended to beincluded within the scope of the invention.

[0043] In determining the amount of lectin to be administered foreffective binding and/or agglutination of the pathogenic microorganismsof STD's, the amount of lectin that might be bound to vaginal tissuesand thereby made unavailable for agglutination of pathogens must beconsidered. In studies on murine vaginal tissue, DBA, LAA, LBA, LCA,LTA, RCA-I, RCA-II, SJA, STA, VGA, and WFA have been found not to bindto the tissue at any stage of the estrus cycle. In contrast, ABA, MPA,PHA-E, PHA-L, Suc-ConA, and WGA bound strongly to vaginal tissues at allstages of the estrus cycle. CSA, GSA-I, GSA-II, HAA, HPA, JAC, PNA, PAA,SBA, Suc-WGA, UEA-I, VFA, and VVA exhibited intermediate degrees ofbinding to murine vaginal tissues. The amount of lectin to beadministered for effective prophylaxis can be determined from therelative binding effect of the various lectins to the pathogen and tothe vaginal tissues. The selection of particular lectins to beadministered will depend on the diseases sought to be prevented ortreated. It is preferred to administer a mixture of lectins, eachselected for best agglutinative efficacy against a particular pathogen.

[0044] The lectins may be administered in any fluid or ointment vehiclesuitable for topical administration of pharmaceutical compounds. Thuscreams, ointments, foams, suppositories, liposomes, ovules and the likemay be formulated in which the selected lectins are dispersed in anon-toxic vehicle suitable for topical and in particular for vaginaladministration. Such vehicles include oil-in-water and water-in-oilemulsions, white petrolatum, hydrophilic petrolatum, lanolin emulsions,polyethylene glycols, cocoa butter and the like. Useful vehicles includeemollient oils such as water-soluble oils, e.g., liquid polyethyleneglycols, which promote complete and uniform distribution of themedicament within the vagina. Representative suitable vehicles include alubricating jelly comprised of water, propylene glycol, hydroxyethylcellulose, benzoic acid and sodium hydroxide, a water-soluble oilcomprised of water, glycerin, propylene glycol, polyquaternium #5,methyl paraben and propyl paraben; a cream comprised of benzyl alcohol,cetearyl alcohol, cetyl esters wax, octyldodecanol, polysorbate 60,purified water, and sorbitan monostearate; and a suppository comprisedof polyethylene glycol (PEG) 18, PEG-32, PEG-20 stearate, benzethoniumchloride, methyl paraben and lactic acid. The lectins can also beincorporated into any conventional controlled release system forreleasing them gradually or in a controlled timed release profile to thesite of intended activity_Such systems are well-known to those skilledin the art and include particles having coatings that dissolve or erodeat different controlled rates in a body fluid, matrices, e.g., polymersfrom which the lectins can diffuse, erodible matrices that releaselectins to the site of intended activity, or the like.

[0045] Thus, the invention encompasses a composition having one or morelectins dispersed in a pharmaceutically acceptable non-toxic vehicle.Such a composition may be in the form of a cream, lotion, ointment,salve, foam, meltable solid, or the like.

[0046] According to the invention, the dispersion, suspension, emulsionor solution of lectins in the vehicle may be applied to the site of alesion on the external genitalia, such as the lesions produced by herpessimplex virus type 1 or type 2, chancroid, genital warts, chancre ofsyphilis, and the like, to prevent the transfer of pathogens. Thelectins may also be introduced into the vagina in order to preventconception or infection by pathogens introduced during sexualintercourse. The amount of lectins to be applied will be an amount thatis effective to prevent conception or infection or substantially reducethe risk thereof. The amounts needed to achieve these goals will dependon the effectiveness of the individual lectins, their affinity for thetarget cell and the like. The effective amounts can be determined by theskilled practitioner by routine experimentation. The lectins can bedelivered to the desired site of activity either as a bolus or in theform of a controlled release composition, as is well-known in the art.Because of their ability to bind pathogenic microorganisms, therebyinterfering with their mobility, attachment/adhesion, growth andreproduction, lectins are also useful in therapy of topical infectionsof the vagina. For those diseases wherein the pathogens grow andreproduce within the lumen of the vagina, administration of lectins,alone or in combination with other antimicrobial materials, can assistin the treatment and cure of the infections.

[0047] Because some of the conventional means of administeringmedications to the vagina have certain drawbacks, as discussed above, itis preferred to incorporate the lectins into a device which will remainin the vagina and dispense the lectins over a prolonged period of timein order to maintain an effective concentration of the lectins in thevagina. Such a device may also be designed to provide a barrier thatwill prevent the access of pathogenic organisms into the uterus and mayalso function as a contraceptive device.

[0048] Thus the lectins to be introduced into the vagina can beincorporated in any conventional vaginal medication-dispensing devicesuch as suppositories, ovules, pessaries and the like, includingcontrolled-release systems as discussed above. The lectins may also beincorporated into conventional contraceptive devices such as diaphragms,cervical caps, vaginal sponges or the like. The lectins may beincorporated into the body of such devices or coated on the surfacethereof, either neat or in a vehicle, e.g., as a dusting powder, or in abinder that provides a coating from which the lectins are released overa period of time. It is not excluded that the lectins may be boundcovalently to the surface of the device.

[0049] The device of the invention is generally a ring of elliptical orcircular cross-section made, e.g., from a biocompatible, nontoxicthermoplastic polymer or polymeric open-cell polyurethane. Bonded to oneside of the ring or molded integral with it is a web of the samematerial.

[0050] A device according to the invention having a ring of ellipticalcross-section is illustrated in FIGS. 1-3, wherein the referencenumerals indicate the same elements in each figure. A ring 102 ofgenerally elliptical cross section constitutes the main structuralmember of the device and is sized to fit comfortably in the vaginalvault surrounding the cervix. To one side of the ring 102 is fastened arelatively thin web 104, preferably made of the same material as thering. In some embodiments the web may be molded integrally with thering.

[0051] FIGS. 4-6 illustrate another embodiment of the invention whereina ring 202, of generally circular cross section, carries a thin web 204spanning the central aperture on one side of the ring.

[0052] The device may be manufactured from any material that has beenshown to be biocompatible with the environment of the vagina and to becapable of holding lectins within its bulk and releasing them slowly tothe surrounding environment. Several materials suitable for thisfunction are already known from the vaginal devices already in use ordisclosed in the technical literature. Consequently, the skilledpractitioner can easily select a suitable material from which to makethe device of this invention. The lectins may also be incorporated intoa thin flexible coating, placed on the ring or web or both, and designedto release the lectins therefrom over a period of time, e.g., bydiffusion out of the coating or by gradual erosion and dissolution ofthe coating in the vaginal environment. The lectins may also be linkedcovalently to the surface of the device.

[0053] The device of the invention is designed to deliver one or morelectins locally in the vagina for:

[0054] 1) contraception, by binding to the glycoproteins, glycolipidsand other glycoconjugates on the surface of sperm and by binding to theglycoproteins, glycolipids, and other glycoconjugates in the seminalfluid, thereby creating an ejaculate with significantly greaterviscosity, and thereby preventing sperm from exiting the ejaculate;

[0055] 2) prophylaxis against various sexually transmitted diseases bybinding to the glycoproteins, glycolipids, and other glycoconjugates onthe surface of the bacterial agent or viral coat of the virus and theglycoproteins, glycolipids, and other glycoconjugates in the seminalfluid thereby preventing the infectious agent from reaching the targettissue;

[0056] 3) prophylaxis against various sexually transmitted diseases bybinding to the glycoproteins, glycolipids and other glycoconjugatereceptor sites on the vaginal stratified squamous epithelium andcervical columnar epithelium, whereby the recognition sites for attackby pathogens are blocked or concealed; and

[0057] 4) treatment of topical infections of the vagina by interferingwith the growth and reproduction of the pathogenic microorganism,thereby hindering their ability to infect healthy cells.

[0058] The device of the invention also operates by providing a physicalbarrier to the direct deposition of ejaculate on the cervix. This designassures that the concentration of protective lectins in the cervicalregion will not be diluted and overwhelmed by the ejaculate. Rather, thesperm and the pathogens present in the ejaculate can only reach thecervical region gradually by diffusion and transport around the outsideof the peripheral ring of the device. This slow transport of the spermand pathogens from the ejaculate to the cervical region assures that thelectins will have an opportunity to bind to all appropriate constituentsof the ejaculate. The presence of the lectins, which will coagulate andinhibit the transport of sperm and pathogens, makes it unnecessary tohave a device that fits tightly either around the cervix or against thewall of the vagina.

[0059] Accordingly, the device of the invention has several advantagesover the vaginal medication and contraceptive devices currentlyavailable:

[0060] 1) It is easily inserted and comfortable to use.

[0061] 2) Because of its position in the top of the vaginal canal, itensures that the lectins are carried down through the vagina.

[0062] 3) Since it is placed next to the cervix it can also deliverlectins targeted to the cervix

[0063] 4) Gradual release of lectins provides a more consistent deliveryover time, thus ensuring more efficient treatment.

EXAMPLE 1

[0064] This example illustrates the utility of various lectins inbinding to certain microorganisms and to seminal plasma, sperm, humanserum and cervical mucus.

[0065] The efficacy of binding of various lectins to human sperm andseminal plasma and cervical mucus, an indicator of the effectiveness ofsuch materials as vaginally-applied contraceptives, was investigated invitro by the following procedures. Similarly the efficacy of lectinbinding to Neisseria gonorrhoeae, the pathogen responsible forgonorrhoea, was investigated by the following in vitro procedures. Suchbinding efficacy is an indication of the capability of such lectins tobind the pathogen and prevent infection when used intravaginally as aprophylactic material.

[0066] Growth of bacteria: A cervical isolate of Chlamydia trachomatisserovar G ATCC VR-878 was grown in 175 cm2 McCoy cell monolayers in thepresence of 2 μg of cycloheximide per ml. The culture medium was 90%Eagle's minimum essential medium-10% fetal calf serum-20 mM HEPES (pH7.3) supplemented with 50 μg of gentamycin sulfate per ml. Elementarybodies were purified by differential centrifugation followed by densitygradient centrifugation in Percoll as described by Newhall et al.(Newhall, W. J., Baheiger, B. and Jones, R. B. 1982, Analysis of thehuman serological response to the proteins of Chlamydia trachomatis,Infection Immunity 38: 1181-1189). The purified elementary bodies werewashed twice in 10 mM HEPES-145 mM NaCl (pH 7.4) and resuspended inbicarbonate buffer (100 mM NaHCO3 containing 0.01% NaN₃, pH 9.5). Thedensity of elementary bodies was adjusted to a McFarland No. 2 standardusing the same buffer. Neisseria gonorrhoeae ATCC 19424 were grown onchocolate agar plates for 48-72 hrs at 37° C. in a CO₂ incubator (5% CO₂and 80% humidity) and were harvested by scraping bacteria from the agarsurface and resuspending the cells in sterile phosphate buffered saline.The cells were washed three times by centrifugation at 5000×g andresuspended in bicarbonate buffer, the density of which was adjusted toa McFarland No. 2 standard (optical density as measured by aspectrometer—0.4 at 650 nm). The cells were stored on ice prior toimmediately testing in the lectin binding assay. Lactobacillus jenseniiATCC 25258 was grown 48-72 hrs at 37° C. in a shaking incubator in MRSbroth at pH 5.5 containing 2% glucose. After incubation, cells werecentrifuged at 5000×g for 10 min and washed twice in phosphate bufferedsaline, and the density was adjusted to a McFarland No. 2 standard withbicarbonate buffer. Haemophilus ducreyi was grown on chocolate agarplates for 72 hrs in a CO₂ incubator (10% CO₂ and 80% humidity) t 31° C.Bacteria were harvested by scraping bacteria from the agar surface andresuspending the cells in sterile phosphate buffered saline. The cellswere washed three times by centrifugation at 5000×g, resuspended inbicarbonate buffer and the cell density adjusted to a McFarland No.2standard. The cells were stored on ice prior to immediately testing inthe pectin binding assay.

[0067] Lectin Binding Assay: Biotinylated lectins were reconstituted inphosphate buffered saline (10 mM sodium phosphate-150 mM NaCl, pH 7.2)and stored in a freezer at −70° C. until used. Microtiter plates washedwith 95% ethanol and dried were coated with bacteria. (Chlamydiatrachomatis or Neisseria gonorrhoeae or Haemophilus ducreyi orLactobacillus Jensenii) by adding 200 μl of a bacterial suspension (inbicarbonate buffer) to each well and incubating overnight at roomtemperature. Wells coated with bacteria were washed three times ineither sodium acetate buffered saline, pH 4.0, containing 0.1% Tweendetergent (ABST) or phosphate buffered saline containing 0.1% Tween(PBST). Lectins defrosted at room temperature were diluted in eachbuffer, and 100 μl of various lectins was added to bacteria-coated wellsat a final concentration of 50 μg/ml. After incubation in a humidchamber at room temperature for 2 hours, wells were washed three timeswith either ABST or PBST followed by the addition to each well of 100 μlof alkaline phosphatase streptavidin (10 μg/ml). After incubation for 1hour at room temperature, wells were washed three times with ABST orPBST and 100 μl of freshly prepared p-nitrophenylphosphate (1 mg/ml) in0.1 M Tris buffer-0.15 M NaCl was added and color development wasquantified with a spectrophotometer at 405 nm.

[0068] Cervical Mucus: A sample of cervical mucus was obtained from ahealthy donor and the gel phase separated by centrifugation. The pelletwas washed three times by centrifugation and the mucin stabilized andalkylated before dialysis against a low ionic strength, pH 8.0 buffer.The cervical mucus was bound to flat-bottomed plates by incubating inbicarbonate coating buffer at 4° C. overnight. The plates were washed toremove unbound ligand. Biotinylated lectins were serially diluted acrossthe plates in the wash buffer and the plates incubated at roomtemperature for 2 hrs. Unbound lectin was removed by washing, and thebound lectins were tagged by incubating with streptavidin-alkalinephosphatase at room temperature for 1 hr. Unbound streptavidin-alkalinephosphatase was removed by washing and the assay completed by addingfreshly prepared p-nitrophenylphosphate (1 mg/ml) in 0.1 M Trisbuffer-0.15 M NaCl) and monitoring the rate of color production.

[0069] Seminal Plasma and Sperm: A sample of ejaculate was donated by ahealthy donor and the seminal plasma (supernatant) removed bycentrifugation and frozen at −20° C. The binding assay was performed inthe same way as for cervical mucus.

[0070] The sperm pellet resulting from centrifugation of the ejaculatewas washed twice and total sperm count determined using a hemocytometer.Sperm were added to plates, left to settle at room temperature for 2 hrsand fixed using glutaraldehyde. The plates were then washed and unboundsites blocked with protein solution and stored at +4° C. until use. Theremainder of the binding assay was performed in the same way as forcervical mucus and seminal plasma.

[0071] Serum: A sample of blood was collected from a healthy donor, theserum separated by centrifugation and stored at −20° C. The bindingassay was performed in the same way as for cervical mucus and seminalfluid.

[0072] Analysis of data: Sigma Plot was used for graphing and curvefitting of binding plots. Velocity of the color-forming reaction versusconcentration of lectin added was plotted. Binding curves were fitted tothe hyperbolic equation f(x)=ax/(b+x) where “x” is the concentration oflectin, “f(x)” is the rate of reaction measured by change in opticaldensity (OD) of the reaction solution per unit time, “a” is theasymptotic value of maximum reaction velocity measured as change inoptical density per minute (represented in the following tables asm_(OD)/min) and “b” is the concentration of lectin where half of maximumbinding occurs (represented in the following tables as [Lectin]_(1/2)max). The binding “quotient” is defined as a/b.

[0073] The data for lectin binding to sperm, seminal plasma, cervicalmucus, human serum, Neisseria gonorrhoeae, and Lactobacillus jenseniiare summarized in the following tables wherein WB signifies weakbinding, NB signifies no binding, and N/A signifies not available. TABLE2 SUMMARY OF BINDING DATA QUOTIENT Seminal Cervical Human Lectin SpermPlasma Mucus Serum ABA WB 0.44 WB WB AL NB NB NB NB BPA 0.60 0.86 20.76 WB CAA 0.46 1.04 7.82 WB ConA 2.59 2.68 1.11 3.29 CPA WB WB WB WB CSA WB0.30 7.30 WB DBA WB WB WB WB DSA 1.09 WB WB WB ECA WB WB WB WB EEA NB NB0.39 NB GNA 0.36 0.58 0.24 WB GSA-I/GSA-II WB WB WB WB HAA NB WB WB WBJacalin 3.43 11.63  21.55  8.93 LAA NB 0.57 WB WB LBA WB WB WB WB LcH7.26 2.58 8.64 1.60 LES WB WB WB WB LOTUS NB 0.94 4.13 MAA NB WB WB NBMPA 2.29 3.17 13.8  1.18 NPA NB NB NB NB PWA WB NB NB NB PHA-L WB WB WBNB PNA WB WB 7.25 NB PSA 3.44 2.70 14.5  1.12 PTAgalactose NB WB 1.31 WBPTAgalNacnb NB NB 1.39 WB RPA 1.28 0.84 0.45 WB SBA NB WB WB NB SJA NBWB WB NB STA NB WB WB NB sWGA 1.32 7.50 WB WB TKA WB 0.87 WB WB UEA-1 WBWB 14.72  WB VPA WB 2.78 5.21 2.02 VRA WB 3.35 WB WB VVA N/A 0.81 WB WBWFA 2.48 1.96 26.24  WB WGA 19.38  4.87 12.77  1.13

[0074] TABLE 3 LECTIN BINDING TO SPERM Max [Lectin]_(1/2 Max) Lectin(m_(OD)/min) (μg/ml) Quotient WGA 155 8 19.38 LcH 196 27 7.26 PSA 141 413.44 Jacalin 103 30 3.43 ConA 57 22 2.59 WFA 67 27 2.48 MPA 48 21 2.29sWGA 41 31 1.32 RPA 120 94 1.28 DSA 63 58 1.09 BPA 67 112 0.60 CAA 33 710.46 GNA 27 74 0.36

[0075] TABLE 4 LECTIN BINDING TO SEMINAL PLASMA Max [Lectin]_(1/2 Max)Lectin (m_(OD)/min) (μg/ml) Quotient Jacalin 93 8 11.63 sWGA 45 6 7.50WGA 112 23 4.87 VRA 208 62 3.35 MPA 57 18 3.17 VFA 125 45 2.7 PSA 100 372.70 ConA 51 19 2.68 LcH 147 57 2.58 WFA 49 25 1.96 CAA 51 49 1.04 LOTUS32 34 0.94 BPA 64 74 0.86 RPA 56 64 0.88 VVA 25 31 0.81 GNA 38 65 0.58TKA 39 45 0.87 LAA 37 65 0.57 ADA 0.44 CSA 25 82 0.30

[0076] TABLE 5 LECTIN BINDING TO CERVICAL MUCUS Max [Lectin]_(1/2 Max)Lectin (m_(OD)/min) (μg/ml) Quotient WFA 656 25 26.24 Jacalin 237 1121.55 BPA 353 17 20.76 UEA-1 265 18 14.72 PSA 58 4 14.50 MPA 138 1013.80 WGA 562 44 12.77 LcH 121 14 8.64 CAA 352 45 7.82 CSA 445 61 7.30PNA 174 24 7.25 VFA 203 39 5.21 LOTUS 194 47 4.13 PTAgalNac 110 79 1.39PTAgalactose 113 86 1.31 ConA 41 37 1.11 RPA 25 56 0.45 EEA 27 70 0.39GNA 13 55 0.24

[0077] TABLE 6 LECTIN BINDING TO HUMAN SERUM Max [Lectin]_(1/2 Max)Lectin (m_(OD)/min) (μg/ml) Quotient Jacalin 134 15 8.93 ConA 79 24 3.29VFA 107 53 2.02 LcH 123 77 1.60 MPA 40 34 1.18 WGA 160 142 1.13 PSA 8475 1.12

[0078] TABLE 7 LECTIN BINDING TO NEISSERIA GONORRHOEAE pH 4 Max[Lectin]_(1/2 Max) Lectin (m_(OD)/min) (μg/ml) Quotient BPA 1190 8214.51 CPA 80 33 2.42 CSA 560 7 80.00 GNA 294 18 16.33 LAA 176 42 4.19LBA 275 14 19.64 LCH 213 176 1.21 LEA 106 7 14.29 MAA 235 56 4.20 MPA159 5 31.80 NPA 299 38 7.87 PSA 55 13 4.23 RPA 233 10 23.30 SBA 414 851.75 STA 194 24 7.57 sWGA 49 0.50 90.00 TKA 178 55 3.24 VVA 411 3137.00 WFA 331 3 110.33 WGA 125 0.78 160.26

[0079] TABLE 8 LECTIN BINDING TO LACTOBACILLUS JENSENII Max[Lectin]_(1/2 Max) Lectin (m_(OD)/min) (μg/ml) Quotient ABA 216 2 108.00BPA 557 57 9.77 GNA 405 12 33.75 Jacalin 148 7 21.14 LBA 334 15 22.27RPA 177 55 3.22 SBA 523 63 8.30 WFA 464 23 20.17 STA 140 19 7.37 LEA 4582 0.55 DSA 26 80 0.33 MPA 2047 328 6.24 ConA 301 7 43.00 sWGA 96 641.50 LAA 136 17 8.00 CSA 624 387 1.61 NPA 425 36 11.81 VVA 260 33 7.88

[0080] In the above tables the affinity of the lectin for a particularsubstrate is inversely proportional to the maximum velocity of thecolor-forming reaction. Consequently, those lectins having a smaller bvalue ([lectin]_(1/2) max) bind more firmly to the substrate. A highbinding efficacy (low m_(OD)/min) is preferable for binding to sperm orseminal plasma for contraceptive purposes or to a pathogen, such asNeisseria gonorrhoeae, whose infections activity is to be inhibited.However, it must be recognized that some microorganisms of the vaginalflora, e.g., Lactobacillus jensenii, are desirable and may even providesome protection against pathogenic organisms. Accordingly, if possible,it is desirable to select a lectin for contraception and/or prophylaxisagainst sexually transmitted diseases that combines great bindingaffinity for the constituents of the male ejaculate or for a pathogenicmicroorganism, but has a lesser, preferably minimal, binding affinityfor beneficial vaginal flora. A skilled practitioner may select the mostefficacious lectins by consulting the data provided in the tables ofthis example.

EXAMPLE 2

[0081] This example illustrates the effectiveness of lectins ininhibiting the infective activity of Chlamydia trachomatis.

[0082]Chlamydia trachomatis serovar G was cultured as described inExample 1, lyophilized lectins were reconstituted in phosphate bufferedsaline (PBS) to a concentration of 1 mg/ml and frozen at −20° C. Thelectins were prepared for testing in the Chlamydia trachomatisinactivation assay by diluting them in Minimum Essential Medium (MEM)with 10 mM HEPES and 50 μg/ml gentamycin sulfate to appropriateconcentrations. Chlamydia trachomatis serovar G elementary bodies wereadded to the diluted lectins and the mixture was incubated for 1.5 hoursat 37° C. After incubation, the Chlamydia-lectin mixture was added tomonolayers of McCoy cells in 15×45 mm shell vials and centrifuged at3500×g for 60 minutes at 37° C. Following centrifugation, the medium inthe vials was removed and 1 ml of fresh Chlamydia overlay medium (withcycloheximide) was added to each vial. The vials were incubated for40-43 hours and the cells were then fixed and stained for Chlamydiatrachomatis using Syva Microtrak™ Chlamydia trachomatis cultureconfirmation reagent.

[0083] Samples of the infected cell culture were then examined under thefluorescence microscope and evaluated for the effect of the lectin onthe infectivity of the microorganism. Table 9 shows the number ofChlamydia trachomatis inclusions per 160×microscopic field on a 12 mmcircular glass coverslip as a percentage of a positive control samplewhich was not exposed to any lectins. WGA (118%) and ConA (121%) showenhanced infectivity of Chlamydia trachomatis serovar G in having moreinclusions per 160×field than the positive control which had not beenexposed to any lectins. In contrast, exposure to Jacalin showssignificantly reduced infectivity of Chlamydia trachomatis serovar G asevidenced by the 65% reduction in the number of inclusions per 160×field(35% of the positive control value). TABLE 9 Lectin ConcentrationInfectivity ABA 150 59 TKA 150 80 WGA 50 118 DSA 50 75 WFA 150 48 VFA150 61 ConA 150 121 Jacalin 150 35 MPA 150 55

[0084] Table 10 shows the results of additional experiments fordetermining the anti-Chlamydia activity of selected lectins. The data inthe table show that at concentrations of 150 μg/ml, the lectinsdesignated HAA, ABA, and RPA significantly reduced infection of McCoycells by C. trachomatis. However, of these three, only the lectindesignated RPA was cytotoxic to McCoy cells. The lectins WGA and ConApotentiated chlamydial infectivity compared to control samples devoid oflectins. TABLE 10 Anti-Chlamydia Activity of Lectins ConcentrationInfectivity (a) Lectin (μg/ml) Exp. 1 Exp. 2 Exp. 3 Exp. 4 HAA 150 40.444.0 42.0 42.1 ABA 150 48.8 62.0 62.3 57.7 RPA 150 59.6 60.0 60.0 59.9WFA 150 73.8 72.9 95.9 80.9 NPA 150 81.4 99.0 69.3 83.2 GNA 150 82.094.2 83.4 86.5 sWGA 100 95.8 75.8 93.6 88.4 LAA 150 86.7 92.3 86.5 88.5LBA 150 88.2 110.0 74.5 90.9 MAA 150 94.4 101.0 82.5 92.6 BPA 150 93.5109.0 101.0 101.0 CSA 150 94.9 124.0 118.0 112.0 LEA 150 110.0 140.0102.0 117.0 DSA 50 124.0 135.0 96.1 118.0 WGA 50 109.0 154.0 144.0 136.0ConA 150 123.0 168.0 164.0 149.0

EXAMPLE 3

[0085] This example illustrates the effectiveness of lectins in blockingthe infectivity of human immunodeficiency viruses Type 1 and 2(HIV-1/HIV-2).

[0086] A number of lectins were evaluated for possible inhibitoryeffects against HIV-1 and HIV-2 replication in primary infected humanT-lymphocyte CEM cells. The effect of lectins on the infectivity ofHIV-1 and HIV-2 toward human lymphocytes was investigated in vitro by astandard technique (Balzarini et al. 1991, Antimicrobial Agents andChemotherapy, March 1991, pages 410-416) wherein the toxicity of thelectins toward the infected cells was determined (human T-lymphocytesCEM/0) and also the ability of the lectins to block the fusion ofinfected cells (HUT-78/HIV-1(III_(B))) with other cells (MOLT/4 clone8). The results of these tests are set forth in Tables 11 and 12 below.The results are expressed in terms of the concentration of lectinsrequired to reduce by 50% the number of viable cells in thevirus-infected cell cultures (EC₅₀) and in the control cell cultures(mock-infected) (CC₅₀), respectively. That is, CC₅₀ is the cytotoxicconcentration without virus and corresponds to lectin concentrationsrequired to reduce by 50% the number of viable cells in thevirus-infected culture. TABLE 11 Anti-Virus Activity of Lectins EC₅₀(μg/ml)^(a) Lectin HIV-1 HIV-2 CC₅₀ ^(b) (μg/ml) GNA 0.80 ± 0.1  1.35 ±0.6  >100 NPA 0.8 ± 0.2 0.9 ± 0.2 >200 ConA 111.5 ± 0.79   1.4 ± 0.77  20 ± 0.71 EEA >0.16 >0.16 0.5 ± 0.4 MPA >0.8 >0.8 8.9 ± 3.0 LCH  11 ±8.2 >100  15 ± 2.9 HAA  15 ± 7.8 11.5  14 ± 5.9 WGA ≧16 ± 6.0  ≧15 ±7.8   13 ± 2.5 PSA  16 ± 6.4 82 ± 32  21 ± 5.7 DSA >20 >20 1.5JAC >20 >20  22 ± 7.4 PHA-L 23 ± 19 >100  17 ± 8.5 PNA >20 >20 88 ± 11VFA 34 ± 25 ≧100 97 ± 22 ABA >100 >100 73 ± 15 CAA >100 >100 ≧140CPA >100 >100 >200 CSA >100 >100 >200 ECA ≧100 ≧100  14 ± 2.5GSA-I >100 >100 >200 GSA-II >100 >100 ±90 LAA >100 >100 >200LBA >100 >100 >200 LEA >100 >100 >200 Lotus >100 >100 ≧90 PAA ≧100≧58 >200 PTA-gal >100 >100 >200 PTA-galNAc >100 >100 >200SJA >100 >100 >200 sWGA >100 >100 >200 SBA 100 >100 ND^(c) TKA >100 >10098 UEA-I >100 >100 >200 VVA >100 >100 >200 WEA >100 >100 >200

[0087] The above data indicate that only a few lectins proved inhibitoryto HIV-1 and HIV-2 replication in primary infected CEM cultures underthe conditions of this experiment. At concentrations ranging from 0.80to 1.5 μg/ml, the lectins designated GNA, NPA and ConA inhibitedvirus-induced cytopathogenicity in CEM cells by 50%; however, the lectindesignated ConA also was found to by cytotoxic to CEM cells at about 20μg/ml.

[0088] It should also be noted that in practice in administering lectinsfor contraceptive, prophylactic, and/or therapeutic use, it is notalways preferred to use the lectin that binds most strongly to thetarget microorganism. For example, it is preferable to use lectins thatwill not stimulate a mitogenic response in the host. TABLE 12 InhibitoryEffect of Lectins on Giant Cell Formation Between HUT-78/HIV-1 (III_(B))and MOLT/4 clone 8 cells EC₅₀ (μg/ml) Compound Individual Values AverageABA >100->100 >100 CAA >100->100 >100 ConA 1.7-9   5.4 ≧ 5.2CPA >100->100 >100 CSA >100->100 >100 ECA >100->100 >100 EEA >4->4 >4GSA-I >100->100 >100 GSA-II >100->100 >100 HAA >100->100 >100JAC >100->100 >100 LAA >100->100 >100 LBA >100->100 >100 LCH 45-45 45LEA >100->100 >100 Lotus >100->100 >100 MPA >100->100 >100PAA >100->100 >100 PHA-L 44-12-44 33 ± 18 PNA >100->100 >100 PSA45-58-58  54 ± 7.5 PTAgal >100->100 >100 PTAgalNac >100->100 >100SJA >100->100 >100 sWGA >100->100 >100 TKA >100->100 >100UEA-I >100->100 >100 UFA >100->100 >100 VVA >100->100 >100WFA >100->100 >100 WGA  20->4  ≧20

[0089] The invention having now been fully described, it should beunderstood that it may be embodied in other specific forms or variationswithout departing from its spirit or essential characteristics.Accordingly, the embodiments described above are to be considered in allrespects as illustrative and not restrictive, the scope of the inventionbeing indicated by the appended claims rather than by the foregoingdescription, and all changes which come within the meaning and range ofequivalency of the claims are intended to be embraced therein

We claim:
 1. A method of treating sexually transmitted infectionscomprising administering to the site of the infection an amount of acomposition containing at least one lectin capable of binding to apathogenic microorganism or to carbohydrate moieties expressed on thesurface of epithelial cells at the site of the infection, said lectinbeing effective to diminish the infective capability of themicroorganism, said lectin being dispersed in a biocompatible non-toxicvehicle.
 2. The method of claim 1 wherein a plurality of lectins isadministered.
 3. The method of claim 1 wherein said disease is selectedfrom the group consisting of gonorrhea, chlamydial infections,lymphogranuloma venereum, syphilis, chancroid, donovanosis, Mycoplasmahominis infections, Mycoplasma genitalium infections, Ureaplasmaurealyticum infections, HIV-1 and HIV-2 infections, HTLV-1 infections,herpes simplex virus type 1 and type 2 infections, Epstein-Barr virusinfections, infections with human papilloma viruses, molluscumcontagiosum, cytomegalovirus infections, viral hepatitis,trichomoniasis, and candidiasis.
 4. The method of claim 3 wherein aplurality of lectin is adminstered.
 5. The method of claim 1 whereinsaid lectin is selected from the group consisting of BPA, CPA, CSA, GNA,LAA, LBA, LCH, LEA, MAA, MPA, NPA, PSA, RPA, SBA, STA, sWGA, TKA, VVA,WFA, and WGA.
 6. The method of claim 5 wherein a plurality of lectins isadministered.
 7. The method of claim 1 wherein said sexually transmitteddisease is infection with Chlamydia trachomatis and said lectin isselected from the group consisting of ABA, TKA, DSA, WFA, VFA, Jacalin,MPA, HAA, WGA, and GNA.
 8. The method of claim 7 wherein a plurality oflectins is administered.
 9. The method of claim 1 wherein said sexuallytransmitted disease is infection with HIV-1 or HIV-2 and said lectin isselected from the group consisting of ConA, EEA, GNA, MPA, and HAA. 10.The method of claim 9 wherein a plurality of lectins is administered.11. The method of claim 1 wherein said sexually transmitted disease isgonorrhea and said lectin is selected from the group consisting of BPA,CPA, CSA, GNA, LAA, LBA, LCH, LEA, NPA, MAA, MPA, NPA, PSA, RPA, SBA,STA, sWGA, TKA, VVA, WFA, and WGA.
 12. The method of claim 11 wherein aplurality of lectins is administered.
 13. The method of claim 1 whereinsaid site of infection is the female or male urogenital tract.
 14. Acomposition for administering lectins to the vagina comprising at leastone lectin dispersed in a pharmacologically acceptable non-toxicvehicle.
 15. The composition of claim 14 containing a plurality oflectins.
 16. The composition of claim 14 wherein said lectin is selectedfrom the group consisting of WGA, LcH, PSA, Jacalin, ConA, AS, WFA, MPA,sWGA, RPA, DSA, BPA, CAA, GNA, VRA, VFA, LOTUS, NPA, VVA, TKA, LAA, ABA,CSA, UEA-1, PNA, PTAgalNac, PTAgalactose, EEA, ORS, STA, PAA, LOA, andLEA.
 17. The composition of claim 16 containing a plurality of lectins.18. A device for administering lectins to the vagina comprising a solidsupport adapted to be inserted into the vagina, said support beingimpregnated with or coated with at least one lectin.
 19. The device ofclaim 18 wherein a plurality of lectins are impregnated therein orcoated thereon.
 20. The device of claim 18 wherein said lectin isselected from the group consisting of WGA, LcH, PSA, Jacalin, ConA, AS,WFA, MPA, sWGA, RPA, DSA, BPA, CAA, GNA, VRA, VFA, LOTUS, NPA, VVA, TKA,LAA, ABA, CSA, UEA-1, PNA, PTAgalNac, PTAgalactose, EEA, ORS, STA, PAA,LOA, and LEA.
 21. The device of claim 20 wherein a plurality of lectinsare impregnated therein or coated thereon.